Obstetrics and Gynaecology - Research Publications

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    Episodic and prospective memory difficulties in 13-year-old children born very preterm
    Stedall, PM ; Spencer-Smith, MM ; Lah, S ; Doyle, LW ; Spittle, AJ ; Burnett, AC ; Anderson, PJ (CAMBRIDGE UNIV PRESS, 2022-04-07)
    OBJECTIVES: Children born very preterm (VP) are susceptible to a range of cognitive impairments, yet the effects of VP birth on long-term, episodic, and prospective memory remains unclear. This study examined episodic and prospective memory functioning in children born VP compared with their term-born counterparts at 13 years. METHOD: VP (n = 81: born <30 weeks' gestation) and term (n = 26) groups were aged between 12 and 14 years. Children completed: (i) standardized verbal and visuospatial episodic memory tests; and (ii) an experimental time- and event-based prospective memory test that included short-term (within assessment session) and long-term (up to 1-week post-session) tasks. Parents completed a questionnaire assessing memory functions in everyday life. RESULTS: The VP group performed worse on all measures of verbal and visuospatial episodic memory than the term group. While there were no group differences in event-based or long-term prospective memory, the VP group performed worse on time-based and short-term prospective memory tasks than term-born counterparts. Parents of children born VP reported more everyday memory difficulties than parents of children born at term, with parent-ratings indicating significantly elevated rates of everyday memory challenges in children born VP. CONCLUSIONS: Children born VP warrant long-term surveillance, as challenges associated with VP birth include memory difficulties at 13 years. This study highlights the need for greater research and clinical attention into childhood functional memory outcomes.
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    Very Preterm Early Motor Repertoire and Neurodevelopmental Outcomes at 8 Years
    Salavati, S ; Bos, AF ; Doyle, LW ; Anderson, PJ ; Spittle, AJ (AMER ACAD PEDIATRICS, 2021-09-01)
    BACKGROUND AND OBJECTIVES: Children born very preterm (<32 weeks' gestation) have more neurodevelopmental problems compared with term-born peers. Aberrant fidgety movements (FMs) are associated with adverse motor outcomes in children born very preterm. However, associations of aberrant FMs combined with additional movements and postures to give a motor optimality score-revised (MOS-R) with school-aged cognitive and motor outcomes are unclear. Our aim with this study was to determine those associations. METHODS: Of 118 infants born <30 weeks' gestation recruited into a randomized controlled trial of early intervention, 97 had a general movements assessment at 3 months' corrected age and were eligible for this study. Early motor repertoire including FMs and MOS-R were scored from videos of infant's spontaneous movement at 3 months' corrected age. At 8 years' corrected age, cognitive and motor performances were evaluated. Associations of early FMs and MOS-R with outcomes at 8 years were determined using linear regression. RESULTS: Seventy-eight (80%) infants with early motor repertoire data had neurodevelopmental assessments at 8 years. A higher MOS-R, and favorable components of the individual subscales of the MOS-R, including the presence of normal FMs, were associated with better performance for general cognition, attention, working memory, executive function and motor function at 8 years; eg, presence of normal FMs was associated with a 21.6 points higher general conceptual ability score (95% confidence interval: 12.8-30.5; P < .001) compared with absent FMs. CONCLUSIONS: Favorable early motor repertoire of infants born <30 weeks is strongly associated with improved cognitive and motor performance at 8 years.
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    Translating antenatal magnesium sulphate neuroprotection for infants born < 28 weeks' gestation into practice: A geographical cohort study
    Doyle, LW ; Spittle, AJ ; Olsen, JE ; Kwong, A ; Boland, RA ; Lee, KJ ; Anderson, PJ ; Cheong, JLY (WILEY, 2021-02-02)
    BACKGROUND: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. MATERIALS AND METHODS: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016-17, and earlier, in 1991-92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016-17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016-17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. RESULTS: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016-17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25-0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016-17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08-0.96; P = 0.043). CONCLUSIONS: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.
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    Impact of moderate and late preterm birth on neurodevelopment, brain development and respiratory health at school age: protocol for a longitudinal cohort study (LaPrem study)
    Cheong, J ; Cameron, KLI ; Thompson, D ; Anderson, PJ ; Ranganathan, S ; Clark, R ; Mentiplay, B ; Burnett, A ; Lee, K ; Doyle, LW ; Spittle, AJ (BMJ PUBLISHING GROUP, 2021-01-01)
    INTRODUCTION: Children born moderate to late preterm (MLP, 32-36 weeks' gestation) account for approximately 85% of all preterm births globally. Compared with children born at term, children born MLP are at increased risk of poor neurodevelopmental outcomes. Despite making up the largest group of preterm children, developmental outcomes of children born MLP are less well studied than in other preterm groups. This study aimed to (1) compare neurodevelopmental, respiratory health and brain magnetic resonance imaging (MRI) outcomes between children born MLP and term at 9 years of age; (2) examine the differences in brain growth trajectory from infancy to 9 years between children born MLP and term; and in children born MLP; (3) examine the relationship between brain development and neurodevelopment at 9 years; and (4) identify risk factors for poorer outcomes at 9 years. METHODS AND ANALYSIS: The "LaPrem" (Late Preterm MRI Study) study is a longitudinal cohort study of children born MLP and term controls, born at the Royal Women's Hospital in Melbourne, Australia, between 2010 and 2013. Participants were recruited in the neonatal period and were previously followed up at 2 and 5 years. This 9-year school-age follow-up includes neuropsychology, motor and physical activities, and lung function assessments, as well as brain MRI. Outcomes at 9 years will be compared between birth groups using linear and logistic regressions. Trajectories of brain development will be compared between birth groups using mixed effects models. The relationships between MRI and neurodevelopmental outcomes, as well as other early predictors of poor 9-year outcomes, will be explored using linear and logistic regression. ETHICS AND DISSEMINATION: This study was approved by the human research ethics committee at the Royal Children's Hospital, Melbourne, Australia. Study outcomes will be disseminated through peer-reviewed publications, conference presentations and social media.
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    Missing out on precious time: Extending paid parental leave for parents of babies admitted to neonatal intensive or special care units for prolonged periods
    Spittle, AJ ; McKinnon, C ; Huang, L ; Burnett, A ; Cameron, K ; Doyle, LW ; Anderson, P ; Baird, M ; Colditz, P ; Cruz, M ; Pussell, K ; Dalziel, K ; Eeles, A ; Newnham, J ; Hunt, RW ; Cheong, J (WILEY, 2021-11-27)
    In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio-economic outcomes for the baby, family and society.
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    Changing consumption of resources for respiratory support and short-term outcomes in four consecutive geographical cohorts of infants born extremely preterm over 25 years since the early 1990s
    Cheong, JLY ; Olsen, JE ; Huang, L ; Dalziel, KM ; Boland, RA ; Burnett, AC ; Haikerwal, A ; Spittle, AJ ; Opie, G ; Stewart, AE ; Hickey, LM ; Anderson, PJ ; Doyle, LW (BMJ PUBLISHING GROUP, 2020-01-01)
    OBJECTIVES: It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN: Prospective longitudinal cohort study. SETTING: The State of Victoria, Australia. PARTICIPANTS: All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES: Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS: Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS: Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.
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    Parcellation of the neonatal cortex using Surface-based Melbourne Children's Regional Infant Brain atlases (M-CRIB-S)
    Adamson, CL ; Alexander, B ; Ball, G ; Beare, R ; Cheong, JLY ; Spittle, AJ ; Doyle, LW ; Anderson, PJ ; Seal, ML ; Thompson, DK (NATURE PUBLISHING GROUP, 2020-03-09)
    Longitudinal studies measuring changes in cortical morphology over time are best facilitated by parcellation schemes compatible across all life stages. The Melbourne Children's Regional Infant Brain (M-CRIB) and M-CRIB 2.0 atlases provide voxel-based parcellations of the cerebral cortex compatible with the Desikan-Killiany (DK) and the Desikan-Killiany-Tourville (DKT) cortical labelling schemes. This study introduces surface-based versions of the M-CRIB and M-CRIB 2.0 atlases, termed M-CRIB-S(DK) and M-CRIB-S(DKT), with a pipeline for automated parcellation utilizing FreeSurfer and developing Human Connectome Project (dHCP) tools. Using T2-weighted magnetic resonance images of healthy neonates (n = 58), we created average spherical templates of cortical curvature and sulcal depth. Manually labelled regions in a subset (n = 10) were encoded into the spherical template space to construct M-CRIB-S(DK) and M-CRIB-S(DKT) atlases. Labelling accuracy was assessed using Dice overlap and boundary discrepancy measures with leave-one-out cross-validation. Cross-validated labelling accuracy was high for both atlases (average regional Dice = 0.79-0.83). Worst-case boundary discrepancy instances ranged from 9.96-10.22 mm, which appeared to be driven by variability in anatomy for some cases. The M-CRIB-S atlas data and automatic pipeline allow extraction of neonatal cortical surfaces labelled according to the DK or DKT parcellation schemes.
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    White matter extension of the Melbourne Children's Regional Infant Brain atlas: M-CRIB-WM
    Alexander, B ; Yang, JY-M ; Yao, SHW ; Wu, MH ; Chen, J ; Kelly, CE ; Ball, G ; Matthews, LG ; Seal, ML ; Anderson, PJ ; Doyle, LW ; Cheong, JLY ; Spittle, AJ ; Thompson, DK (WILEY, 2020-02-21)
    Brain atlases providing standardised identification of neonatal brain regions are key in investigating neurological disorders of early childhood. Our previously developed Melbourne Children's Regional Infant Brain (M-CRIB) and M-CRIB 2.0 neonatal brain atlases provide standardised parcellation of 100 brain regions including cortical, subcortical, and cerebellar regions. The aim of this study was to extend M-CRIB atlas coverage to include 54 white matter (WM) regions. Participants were 10 healthy term-born neonates that were used to create the initial M-CRIB atlas. WM regions were manually segmented based on T2 images and co-registered diffusion tensor imaging-based, direction-encoded colour maps. Our labelled regions imitate the Johns Hopkins University neonatal atlas, with minor anatomical modifications. All segmentations were reviewed and approved by a paediatric radiologist and a neurosurgery research fellow for anatomical accuracy. The resulting neonatal WM atlas comprises 54 WM regions: 24 paired regions, and six unpaired regions comprising five corpus callosum subdivisions, and one pontine crossing tract. Detailed protocols for manual WM parcellations are provided, and the M-CRIB-WM atlas is presented together with the existing M-CRIB cortical, subcortical, and cerebellar parcellations in 10 individual neonatal MRI data sets. The novel M-CRIB-WM atlas, along with the M-CRIB cortical and subcortical atlases, provide neonatal whole brain MRI coverage in the first multi-subject manually parcellated neonatal atlas compatible with atlases commonly used at older time points. The M-CRIB-WM atlas is publicly available, providing a valuable tool that will help facilitate neuroimaging research into neonatal brain development in both healthy and diseased states.
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    The causal effect of being born extremely preterm or extremely low birthweight on neurodevelopment and social-emotional development at 2 years
    Olsen, JE ; Lee, KJ ; Spittle, AJ ; Anderson, PJ ; Doyle, LW ; Cheong, JLY (WILEY, 2021-09-12)
    AIM: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social-emotional development at 2 years' corrected age. METHODS: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term-born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development-3rd edition and the Infant-Toddler Social and Emotional Assessment. Delay was defined as <-1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. RESULTS: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social-emotional competence (4.1 [1.6, 10.2]). CONCLUSION: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social-emotional competence at 2 years' corrected age. Close developmental surveillance, including social-emotional development, is recommended.